ArticlemedRxiv : the preprint server for health sciences2024
Data-driven risk/benefit estimator for multiple sclerosis therapies.
Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Multiple sclerosis (MS) disease-modifying treatments (DMTs) are tested in patients preselected for favorable risk/benefits ratios but prescribed broadly in clinical practice. We aimed to establish data-driven computations of individualized risk/benefit ratios to optimize MS care. Methods: We derived determinants of DMTs efficacy on disability progression from re-analysis and integration of 61 randomized, blinded Phase 2b/3 clinical trials that studied 46,611 patients for 91,787 patient-years. From each arm we extracted 80 and computed 30 features to identify and adjust for biases, and to use in multiple regression models. DMTs mortality risks were estimated from age mortality tables modified by published hazard ratios. Findings: Baseline characteristics of the recruited patients determine disability progression rates and DMTs efficacies with high effect sizes. DMTs efficacies increase with MS lesional activity (LA) measured by relapses or contrast-enhancing lesions and decrease with increasing age, disease duration and disability. Unexpectedly, as placebo arms' relapse rate rapidly declines with trial duration, efficacy of MS DMTs likewise decreases quickly with treatment duration. Conversely, DMTs morbidity/mortality risks increase with age, advanced disability, and comorbidities. We integrated these results into an interactive personalized web based DMTs risk/benefit estimator. Interpretation: Results predict that prescribing DMTs to patients traditionally excluded from MS clinical trials causes more harm than benefit. Treatment with high efficacy drugs at MS onset followed by de-escalation to DMTs that do not increase infectious risks would optimize risk/benefit. DMTs targeting mechanisms of progression independent of LA are greatly needed as current DMTs inhibit disability caused by LA only.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.